Beauty from within

In This Section

May 2018

“Beauty from within” refers to the growing nutricosmetics market, which seeks to restore skin youthfulness through supplements and functional foods and beverages.

Popular nutricosmetic ingredients include collagen peptides, astaxanthin, tomato and rosemary extracts, and resveratrol.

Although some ingredients show promising results in preclinical and clinical studies, larger, better-designed clinical trials are needed to establish effectiveness.

Since ancient times, beauty and youthfulness have been inexorably linked. Yet the world’s population is aging: According to predictions from the United Nations, by 2050 21% of the global population will be aged 60 years or older, compared with 10% in 2000 and 8% in 1950 (https://tinyurl.com/UN-aging, 2001). Along with the more serious health concerns that often accompany older age, many people over 40 worry about changes in their appearance such as greying or thinning hair, wrinkles, and sagging skin. They may even resort to expensive and invasive procedures such as cosmetic surgery or the injection of botulinum toxin (BOTOX) or dermal fillers. But what if youthfulness could be restored simply by taking a daily dietary supplement or sipping a “beauty beverage”?

Such is the promise of the booming nutricosmetics industry, which seeks to restore “beauty from within” through a variety of ingestible skin-, hair-, and nail-boosting supplements. The global market for nutricosmetics reached US $5.13 billion in 2016 and is expected to grow at a compound annual growth rate (CAGR) of 5% between 2017 and 2025 (Transparency Market Research, 2017). In addition to capsule and tablet forms, nutricosmetics are commonly available as powders that can be added to water, juice, or smoothies, and as confectionery items such as chocolates, bars, or gummies. Although conclusive scientific evidence for the efficacy of most nutricosmetics is lacking, promising in vitro, animal, and human data highlight the potential of beauty from within.

Beauty food

Beauty from within is not a novel concept for the Asian market, where the movement has its origins. In Asia, and particularly in Japan, nutricosmetics such as collagen are commonly found in foods and beverages including tea, cookies, chocolate, coffee, and water. The acceptance of nutricosmetics is generally higher in Asia than in Europe or the United States because many nutricosmetic ingredients, such as green tea and bone broth, are linked to traditional Asian medicine (Gunn, L., and Creasy, P., https://tinyurl.com/nutrition-beauty, 2017a). In general, EU and US consumers tend to be more skeptical of the idea of “beauty foods” and are more likely to demand scientific backing for such claims (Gunn, L., and Creasy, P., https://tinyurl.com/nutrition-collagen, 2017b).

Similar to Asia, the Latin American market is highly receptive to the concept of beauty from within. From 2012 to 2016, Latin America showed the fastest growth in new collagen product launches at 33% CAGR, followed by Asia at 23% (Innova Market Insights, 2017). In contrast, North America and Europe had much slower rates of growth in product launches containing collagen, with CAGRs of 16% and 11%, respectively.

Different markets have different priorities for beauty from within products. In Asia, the focus is often skin whitening, whereas in the United States and Europe, consumers desire UV protection and wrinkle-smoothing products (Gunn, L., and Creasy, P., https://tinyurl.com/nutrition-regional, 2017c). Although beauty beverages predominate in Asia, nutricosmetics in the form of tablets, soft-gels, or capsules are more popular in the United States and Europe.

Aging skin

Skin aging results from both intrinsic and extrinsic factors (Spiro, A., and Lockyer, S., http://dx.doi.org/10.1111/nbu.12304, 2018). Intrinsic skin aging is genetically determined and is influenced by individual skin properties and changing hormone levels as a person ages. Extrinsic aging is caused by environmental factors such as sun exposure, pollution, smoking, and nutrition. Most aging-related changes in the skin can be traced to a lifetime of exposure to the sun. UV rays penetrate the skin and trigger the production of reactive oxygen species and matrix metalloproteinases that degrade collagen, the main structural protein in the extracellular matrix of connective tissues such as skin, cartilage, and bone. After age 30, collagen degrades at a rate of 1-2% per year (Shuster, S., et al., https://doi.org/10.1111/j.1365-2133.1975.tb05113.x, 1975). The breakdown of collagen and elastic fibers in the dermis contributes to thinning, sagging, wrinkling, and loss of elasticity in the skin (Fig. 1). In addition, UV radiation damages DNA in skin cells and accelerates the degradation of hyaluronic acid, a glycosaminoglycan important for retaining moisture in the skin.

Most topical cosmetic products cannot penetrate past the epidermis, the outermost layer of the skin. In contrast, if nutricosmetics are sufficiently bioavailable, they can circulate throughout the body, allowing them to reach the dermis where they can have more profound effects on skin structure. “Topical applications affect only the epidermis, and those results are generally more superficial and temporary,” says Lara Niemann, Marketing Director for the Americas at GELITA USA, a manufacturer of collagen peptides with US headquarters in Sergeant Bluff, Iowa. “When ingested orally, collagen peptides affect the dermal layer of the skin, so it really is beauty from within.”

Trending ingredients

For decades, physicians have recognized the value of micronutrients such as vitamin C, vitamin A, zinc, and biotin for skin health because dietary deficiencies can cause skin conditions, among other problems. In addition, antioxidants, such as vitamins E and C, have long been recommended to mitigate oxidative damage in skin, although consistent evidence for their efficacy is lacking. The current crop of popular nutricosmetics includes more complex ingredients harvested from natural sources, such as collagen peptides, astaxanthin, tomato and rosemary extracts, and resveratrol.

Collagen peptides

Collagen is the most abundant protein in humans, comprising about 30% of the protein in the body and 75% of the protein in skin. However, consuming bone broth or other products containing whole collagen is likely ineffective for boosting collagen in the skin. The digestive process breaks whole collagen into fragments of various sizes that are not specifically targeted to skin cells. Therefore, some companies have developed specific collagen peptides that they claim survive digestion and localize to the skin.

GELITA is a producer of gelatin, collagen, and collagen peptides, with worldwide headquarters in Eberbach, Germany (www.gelita.com). The company extracts collagen from bovine and porcine bone and skin, which are byproducts of the meat industry. The collagen is partially hydrolyzed to produce gelatin, a gelling agent used in marshmallows, gummies, and other foods. By treating the hydrolyzed collagen with proprietary enzymes, GELITA scientists produce specific collagen peptides with unique functions. They can then isolate particular peptides or mixtures of peptides. “GELITA has a comprehensive portfolio of bioactive collagen peptides, all of which have been optimized to target different cells of the body,” says Niemann, “Our product VERISOL targets cells in the dermis for skin health. Other products target osteoblasts for bone health, or chondrocytes and the extracellular matrix of joint cartilage for joint health.”

According to Niemann, the collagen peptides bind to specific receptors on the surfaces of cells. For example, the collagen peptides in VERISOL bind to receptors found only on dermal fibroblasts, targeting the peptides to the skin. The receptors recognize the collagen peptides as collagen degradation products. The binding of the collagen peptides to the receptors stimulates the cells to produce more collagen, as well as other extracellular matrix components, to counteract the perceived collagen degradation. The collagen peptides also provide cells with amino acid building blocks to produce more collagen.

Critics have argued that collagen peptides are degraded into individual amino acids upon digestion and therefore could not exert specific effects on skin cell receptors. An upcoming article in the June 2018 issue of Inform will describe how researchers demonstrated that the ingestion of collagen hydrolysate increased blood plasma levels of bioactive collagen peptides, such as prolyl-hydroxyproline, in humans (original research in Iwai, K., et al., https://doi.org/10.1021/jf050206p, 2005).

Animal studies suggest that collagen peptides have beneficial biological effects on skin (reviewed in Proksch, E., et al., https://doi.org/10.1159/000351376, 2014). In one study, ingested collagen peptides increased the size and density of dermal fibroblasts and increased the density of collagen fibers in pig skin. In rats, collagen peptides significantly increased collagen production and reduced the expression of matrix metalloproteinase-2, an enzyme that degrades collagen.

Several clinical trials of collagen peptides have been conducted in humans. In a double-blind, placebo-controlled trial of GELITA VERISOL, 69 women aged 35–55 years were randomized to receive 2.5 g VERISOL, 5 g of VERISOL, or a placebo once daily for 8 weeks (Proksch, E., et al., https://doi.org/10.1159/000351376, 2014a). The women consumed VERISOL as a powder dissolved in water or another cold liquid. Relative to the placebo, both doses of VERISOL showed significant improvements in skin elasticity, which was measured by the extension of skin in response to a suction vacuum. After 8 weeks, the mean increase in skin elasticity was 7% for both of the VERISOL groups, with some women experiencing as much as 30% increased elasticity. There were no statistically significant changes from placebo in skin hydration, transepidermal water loss, or skin roughness. However, this study was conducted on skin of the inner forearm, which makes it difficult to extrapolate the results to facial skin.

The same researchers conducted another double-blind, placebo-controlled study of VERISOL in 114 women aged 45–65 years, this time examining wrinkles in the eye area (“crow’s feet”) (Proksch, E., et al., https://doi.org/10.1159/000355523, 2014b). The women were randomized to receive either 2.5 g VERISOL or a placebo once daily for 8 weeks. After 8 weeks, the VERISOL group had a mean 20.1% reduced eye wrinkle volume compared with placebo (Fig. 2). The maximum reduction in eye wrinkle volume was 49.9%. Four weeks after the last dose, the VERISOL group still showed a mean 11.5% reduction in eye wrinkle volume, suggesting that the effects were relatively long-lasting.

The researchers also examined the amounts of collagen, elastin, and fibrillin in the skin of a subset of the participants by inducing a blister on the forearm with suction and then collecting the fluid with a syringe. They found that the amount of procollagen type 1 (one of two types of collagen proteins that combine to make a collagen fibril) increased by 65% after 8 weeks in the VERISOL group compared with the placebo group. Elastin content increased 18% compared with placebo, whereas there was no significant difference between groups in the amount of fibrillin (another extracellular matrix protein found in skin).

A recent double-blind, placebo-controlled study examined the effects of collagen peptides from a different supplier, Nitta Gelatin Inc. (Osaka, Japan), on facial skin (Inoue, N., et al., https://doi.org/10.1002/jsfa.7606, 2016). Nitta’s Wellnex collagen peptides are enriched in two key dipeptides, prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly). In vitro studies have shown that these dipeptides enhance the proliferation of dermal fibroblasts. Pro-Hyp also chemically attracts dermal fibroblasts and increases their production of hyaluronic acid. The study included 85 Chinese women who consumed 5 g daily of Wellnex collagen peptides, which were ingested orally in hot milk, coffee, or other beverages, for 8 weeks. A mixture of collagen peptides containing a high ratio of Pro-Hyp and Hyp-Gly significantly improved facial skin moisture, elasticity, wrinkles, and roughness compared with the placebo.

In addition to possible benefits for facial skin, collagen peptides may help improve the appearance of cellulite—the skin dimpling of the thighs and buttocks that affects 85% of the global female adult population (Schunck, M., et al., https://doi.org/10.1089/jmf.2015.0022, 2015). A double-blind, placebo-controlled study examined the effects of VERISOL collagen peptides on 105 normal and overweight women aged 24–50 years with moderate cellulite. The researchers found that a 2.5 g daily dose of VERISOL collagen peptides administered for 6 months significantly improved the cellulite score, reduced skin waviness on thighs, and increased dermal density compared with the placebo. The effects were more pronounced for normal-weight women: These women showed a mean reduction of 9% in cellulite score compared with placebo, versus a mean 4% reduction in cellulite score for overweight women. The researchers proposed that the improvements in cellulite appearance could result from increased synthesis of dermal connective tissue, which improved skin strength and elasticity.

A recent open-label clinical trial suggested that collagen peptides also improve the health and appearance of fingernails (Hexsel, D., et al., https://doi.org/10.1111/jocd.12393, 2017). Twenty-five participants took 2.5 g of VERISOL once daily for 24 weeks. At the end of the treatment period, nail growth rate had increased by 12%, and the frequency of broken nails had decreased by 42%. Nail brittleness improved in 64% of participants, and 80% of participants said the treatment improved the appearance of their nails. However, this study must be repeated with larger numbers, blinding, and a placebo group before definitive conclusions can be made.

Collagen peptides have properties that make them highly functional as ingredients for food and beverage formulations, says Niemann. “They are neutral in taste, neutral in color, highly dissolvable, and dispersible, so that lends them very well to any number of different applications,” she says. These “functional food” applications include beverages, dairy products such as yogurts and smoothies, bars, and gummies.

Astaxanthin

Another popular ingredient in the beauty from within category is astaxanthin, a carotenoid antioxidant. Astaxanthin (3,3’-dihydroxy-β-carotene-4,4’-dione; Fig. 3) is the red-orange pigment that gives shrimp, lobster, and salmon their brilliant color. The richest natural source of astaxanthin is the microalga Haemotococcus pluvialis.

FIG. 3: Structure of astaxanthin Credit: Wikimedia Commons

“Microalgae have been on the planet for billions of years and have managed to survive all kinds of climactic changes and disasters using very unique survival mechanisms,” says Efrat Kat, Vice President of Marketing and Sales at Algatechnologies Ltd., in Ketura, Israel (www.algatech.com). One of these survival mechanisms, which involves astaxanthin, allows microalgae to survive during bouts of intense sunlight. Under these conditions, H. pluvialis forms cysts, during which the cells produce high levels of astaxanthin to help cope with environmental stress (Fig. 4). “The role of the astaxanthin is to protect the photosynthetic apparatus of the algae from sun radiation and other environmental stress,” says Kat. “Exactly the same as astaxanthin protects the algae, it can protect our skin.”

The chemical structure of astaxanthin allows the molecule to span cellular membranes. Hydrophilic head groups project into the cytoplasm and extracellular environment, whereas the nonpolar carbon chain resides amidst the fatty acid tails in the phospholipid bilayer. This structure facilitates electron transfer from free radicals along the conjugated double bonds of the molecule to an acceptor molecule, such as vitamin C. In human dermal fibroblasts, astaxanthin attenuates the UVA-induced increase in expression of two enzymes that break down the collagen and elastin networks in the dermis—matrix metalloproteinase-1 and skin fibroblast elastase (Suganuma, K., et al., https://doi.org/10.1016/j.jdermsci.2010.02.009, 2010).

Algatechnologies produces astaxanthin from H. pluvialis cultivated in about 600 km (373 miles) of closed tubular photobioreactors exposed to natural sunlight. The Algatechnologies production facility is located in the Arava Desert of southern Israel. “It’s one of the most arid places on earth, and we have very high sun radiation year round,” says Kat. She notes that Algatechnologies has identified a species of H. pluvialis, named the “Arava species,” that produces particularly high amounts of astaxanthin under these conditions. “If you take the same species and grow it in a different location or use a different technology, you will not get the same results,” she says. “It’s a combination of the species, the technology, and the location that gives us the best results.” Algatechnologies scientists extract astaxanthin from the cells using supercritical carbon dioxide technology to ensure a highly pure, solvent-free product known as AstaPure.

Few high-quality clinical trials on the skin benefits of astaxanthin have been reported. In a randomized, double-blind, placebo-controlled study of 36 healthy males aged 20–60 years, supplementation with 6 mg AstaREAL astaxanthin (Tokyo, Japan) for 6 weeks improved the area and volume of crow’s feet wrinkles by about 16% and 15%, respectively, compared with the placebo (Tominaga, K., et al., Acta Biochim. Pol 59, 43–47, 2012). In addition, skin elasticity improved by 5%, and transepidermal water loss decreased by almost 20% in the AstaREAL group compared with placebo.

In another study, researchers examined changes in systemic oxidative stress and residual skin surface components upon astaxanthin supplementation in 31 volunteers aged 40–80 years (Chalyk, N. E., et al., https://doi.org/10.1016/j.nutres.2017.10.006, 2017). The volunteers consumed 4 mg per day of astaxanthin (Lycotec Ltd., Cambridge, UK) for 4 weeks. Then researchers took blood samples and measured levels of plasma malondialdehyde (MDA), which is a biomarker of systemic oxidative stress. They found that the mean MDA concentration in blood plasma decreased from baseline by 11.2% on day 15 and by 21.7% on day 29 of astaxanthin supplementation.

Residual skin surface components (RSSC) consist of a mixture of lipids produced by sebaceous glands and epidermal cells, desquamated corneocytes, and sweat. The researchers found that at the end of the study, participants had decreased levels of corneocyte desquamation and microbial stress—two characteristics that are associated with younger skin. These differences from baseline were more pronounced in obese subjects, possibly because a higher body mass index (BMI) has been associated with increased oxidative stress. Therefore, obese people may show a stronger response to the antioxidant effect of astaxanthin. This study was limited by a small sample size and no placebo group.

According to Kat, Algatechnologies offers a variety of different delivery forms of astaxanthin. “We can supply astaxanthin as a carotene oil form, powder, tablets, water-dispersible powder, or emulsion,” she says. “We try to offer all of the possible solutions so our customers can develop almost any type of product.” Kat notes that because astaxanthin is a dark red pigment, it is difficult to incorporate the high dosages found in oral supplements into topical creams. “To keep the cream at the desired color, you must use a very low dosage of astaxanthin,” she says.

Cambridge Chocolate Technologies (Cambridge, UK) has produced a dark chocolate bar that is enriched with astaxanthin. One bar contains about 11.4 mg astaxanthin—roughly the same amount as 300 g salmon. In addition to astaxanthin, the cocoa flavanols in the chocolate act as antioxidants, the developers say.

Tomato/rosemary extracts

A synergistic effect between lycopene from tomatoes and carnosic acid from rosemary underlies Lycoderm, Lycored’s proprietary carotenoid blend for skin health (Fig. 5). Lycored, with headquarters in Be’er Sheva, Israel, was established in 1995 “with a vision to bring the health benefits of the tomato to people around the world,” says Golan Raz, head of the Global Health Division at Lycored. “The company developed proprietary tomato breeds together with unique extraction and validation methods.” In addition to Lycoderm, Lycored offers supplements for heart health (Cardiomato), menopause (Lycofem), eye health (Lycoinvision), and prostate health (Lycopro).

FIG. 5: Lycoderm, a combination of standardized tomato and rosemary extracts formulated to help protect skin from UV damage and other environmental stress. Credit: Lycored

Lycoderm’s tomato extract contains the carotenoids lycopene, phytoene, and phytofluene, which function as antioxidants. Carnosic acid from rosemary is also a potent antioxidant. In May 2017, Lycored was awarded the NutraIngredients Award for Best University Research for a study published in the British Journal of Dermatology. The placebo-controlled, double-blind, randomized, cross-over study examined the ability of Lycoderm, lutein, or a placebo to dampen the expression of three genes that are induced by UV radiation: HO1 (an indicator of oxidative stress), ICAM1 (involved in skin inflammation), and MMP1 (involved in collagen breakdown) (Grether-Beck, S., et al., https://doi.org/10.1111/bjd.15080, 2017).

In this study, 65 healthy volunteers aged 18–60 years were allocated to four treatment groups. Each group either started with the active treatment (Lycoderm or lutein) for 12 weeks and then switched to the placebo for 12 weeks, or vice versa. At the beginning and end of each treatment phase, the participants’ skin was mildly irradiated with UV light, and 24 hours later, skin samples were taken for gene expression analysis by reverse transcriptase–polymerase chain reaction (RT-PCR).

Lycoderm inhibited the UV-induced upregulation of HO1, ICAM1, and MMP1, in either crossover sequence (before or after placebo). In contrast, lutein inhibited UV-induced gene expression if it was taken in the first sequence (before placebo), but worked less well in the second sequence (after placebo). The researchers do not currently know the mechanism behind this observation, but consistent with previous studies, the combined effects of tomato phytonutrients appear to be stronger than any one phytonutrient for protection from UV skin damage. UVA1 radiation is known to generate singlet oxygen, which initiates radiation-induced gene expression. Carotenoids, especially lycopene, can quench singlet oxygen.

Resveratrol

Resveratrol, a phenol found in grapes, berries, peanuts, and Japanese knotweed, has antioxidant and anti-inflammatory properties (Fig. 6). In pre-clinical studies, resveratrol was shown to inhibit the UV-induced activation of pro-inflammatory transcription factors and activate enzymes and transcription factors that combat reactive oxygen species (Farris, P., et al., J. Drugs Derm. 12, 1389–1394, 2013). Resveratrol may also play a role in mitochondrial biogenesis. Some have proposed that resveratrol, famously found in red wine, underlies the so-called French paradox: the observation that despite eating a diet rich in saturated fats, French people have a low incidence of heart disease. “Although resveratrol is naturally found in red wine, it’s only in very small amounts,” says Clare Panchoo, sales director for Evolva (Reinach, Switzerland) in Europe, the Middle East, and Africa. “You’d have to drink around 75 glasses of wine in one day to get an effective dose of resveratrol.”

FIG. 6: Structure of resveratrol Credit: Wikimedia Commons

Although resveratrol is unlikely to explain the French paradox, the molecule has been studied widely for possible effects on heart disease, cancer, and life extension. Recently, researchers have begun to explore the use of resveratrol for skin health. Some small-scale studies have hinted at effects of topical resveratrol in anti-aging, skin whitening, acne, and psoriasis. Thus far, no studies have reported effects of ingested resveratrol by itself on skin health, although one study examined a dietary supplement containing both resveratrol and the polyphenol procyanidin (Buonocore, D., et al., https://doi.org/10.2147/CCID.S36102, 2012). The researchers found that the combined supplement decreased systemic oxidative stress, improved skin moisturization and elasticity, diminished skin roughness and depth of wrinkles, and decreased the intensity of age spots.

Evolva produces a food-grade form of resveratrol, called Veri-te, through a yeast fermentation process. The product is off-white, odorless, and colorless. “Today, resveratrol is mainly available in supplement form, but Evolva’s Veri-te brand is focused on helping expand the application possibilities,” says Panchoo. “Currently, it is challenging to incorporate resveratrol into functional beverages because it is not soluble. This spring, the Veri-te brand will launch an ingredient innovation that will enable cold-water dispersion of resveratrol.”

Thus far, the biggest challenge facing ingested resveratrol has been its poor in vivo bioavailability (Ndiaye, M., et al., https://doi.org/10.1016/j.abb.2010.12.030, 2011). In mammals, resveratrol is quickly metabolized in the liver, often within 30–60 minutes of ingestion. “More than 10,000 studies on resveratrol have been published, including 200 clinical trials, and many have identified the beneficial effects of oral resveratrol for indications ranging from cognitive and bone health to cardiovascular and skin health,” says Panchoo. “Therefore, resveratrol might have low bioavailability, but it has high bioactivity.”

The future of beauty?

Although beauty foods, drinks, and supplements require more research to firmly establish their benefits, mechanisms, and possible risks, beauty from within is likely to be an attractive and intuitive concept for many consumers. An open question is whether people will be satisfied with or even notice the relatively modest improvements (usually on the order of 10–20%) demonstrated thus far for skin characteristics such as moisture, elasticity, and wrinkle depth. In any case, consumers should not expect miraculous or instantaneous transformations. “We know it takes a while for the skin’s metabolism to slow and wrinkles to form, so it’s only natural that supplementation to improve these things is going to take time, as well,” says Niemann. “It’s not that you take VERISOL collagen peptides today, and your skin looks better tomorrow.”

Other ingredients not discussed in this article have shown promise as skin-boosting supplements in some studies, such as probiotics, prebiotics, coenzyme Q10, and hyaluronic acid. It is likely that a combination of ingredients, rather than any one, in both topical and supplement forms will provide the greatest benefits to skin health. “A nice trend we see developing is the combination of nutritional and topical products into one holistic approach,” says Raz. “This trend is well supported by a growing awareness among consumers of the importance of a multi-factorial approach when it comes to skin’s health, longevity, and beauty. One aspect, no matter how sophisticated it is, will not provide the long-term foundation for lasting health and beauty.”